For use in pharmacotherapy, a drug delivery system (DDS) is intended to aid the delivery of medicine to a target site within a body to bring about a therapeutic effect. If a medicine is excreted too fast from the body due to its low absorption or bioavailability rates, a DDS may be used to modify the drug release profile. Medicines with serious side effects need to be delivered to target tissues or cells only. For example, many currently available anticancer agents exhibit cytotoxicity on normal cells as well as on cancerous cells. The substantial delivery of anticancer agents to cancerous cells or tissues would reduce the agony and inconvenience of cancer patients during treatment.
Since the first use thereof in the 1960s, liposomes have been widely studied for their use in DDS. Advances in liposome research have constructed, in conjugation with polymers such as polyethylene glycol (PEG) studding the outside of the membrane, so-called stealth liposomes, which can avoid detection by the body's immune system. The PEG coating allows for longer circulatory half-life for the drug delivery mechanism. In practice, DOXIL, a pegylated liposome-encapsulated form of doxorubicin, has been developed. However, liposomes and stealth liposomes themselves cannot deliver drugs to target cells or tissues because they lack the ability to recognize the target cells or tissues. To allow liposomes to bind to a specific target, studies have recently been directed toward the impartment of targeting ligands, such as monoclonal antibodies, to liposomes, but none of them have yet passed clinical tests and been successfully commercialized.
In lieu of artificially synthesized liposomes consisting of lipids, naturally existing cellular membranes are used to develop delivery systems. A method of drug delivery using minicells secreted from microorganisms grown in drug-containing media is disclosed [WO 2005/079854, “Compositions and methods for targeted in vitro and in vivo drug delivery to mammalian cells via bacterially derived intact minicells”]. Minicells, usually comprised of bacterial cell membrane, are liable to contain toxic materials, for example, endotoxins (lipopolysaccharides) present in the outer membrane if derived from Gram-negative bacteria, or peptidoglycans present in the cell wall if derived from Gram-positive bacteria, so that they may cause various side effects such as systemic inflammation, sepsis, etc.
A protoplast is a bacterial, archaeal, fungal, plant cell that had its cell wall completely removed. The removal of the cell wall may resort to enzymes such as lysozyme for bacterial or archaeal cells, chitinase for fungal cells, and cellulase, pectinase and/or xylanase for plant cells. Protoplasts can be used to study membrane biology, including the uptake of macromolecules and viruses. In addition, protoplasts are applied to DNA transformation for making genetically modified organisms. Protoplasts may also be used for plant breeding, using a technique called protoplast fusion. However, microvesicles derived from protoplasts have not yet been reported, and neither has the applications thereof been, thus far.